Overview of the Schmidt Laboratory

The Schmidt Laboratory at Massachusetts General Hospital pursues "bedside-to-bench" mechanistic investigations of sepsis and septic organ injury. We are particularly interested in the function and fate of the endothelial and epithelial glycocalyces during health and critical illness. Using human and animal studies, we identified that sepsis-associated degradation of the endothelial glycocalyx induces local vascular dysfunction (leading to acute respiratory distress syndrome [ARDS] and acute kidney injury) while simultaneously releasing circulating heparan sulfate fragments that penetrate the hippocampus and impair cognition in sepsis survivors.

Our interests extend beyond the vasculature: we have identified the presence and structure of an alveolar epithelial glycocalyx, defined its importance to surfactant homeostasis, and determined the impact of its degradation on secondary bacterial pneumonia pathogenesis and ARDS outcomes. 

Our laboratory is proud of the numerous successes of its trainees, who have pursued impactful research under F31, F32, K08 (NHLBI, NIA), R03, and foundation support, including the American Heart Association. 

Research Team

Eric Schmidt, MDEric Schmidt, MD, Principal Investigator

Dr. Schmidt is a physician-scientist at Mass General, where he serves as the division chief of Pulmonary and Critical Care Medicine. After graduating from medical school at the University of Pittsburgh in 2001, Dr. Schmidt completed residency, chief residency, and pulmonary and critical care fellowship at the Johns Hopkins Hospital. In 2009, he joined the faculty of the University of Colorado and the Denver Health Medical Center. In 2022, he was recruited to Mass General and Harvard Medical School. He is a Fellow of the American Thoracic Society, an elected member of the American Society for Clinical Investigation, an Associate Editor of the American Journal of Physiology—Lung Cellular and Molecular Physiology, and a standing member of the National Institutes of Health (NIH)/Center for Scientific Review Surgery, Anesthesiology, and Trauma study section. 

Yimu Yang, MD, PhDYimu Yang, MD, PhD

Dr. Yang is a PhD scientist with nationally recognized expertise in the modeling of sepsis and lung injury. While initially focused on the endothelial glycocalyx in the pulmonary circulation, he has expanded his interest to determine the relevance of heparan sulfate to pulmonary fibrosis. On weekends, he enjoys taking in fresh air from the shady forests and lofty summits traversed by local beloved trails. 

Kaori Oshima, PhDKaori Oshima, PhD

Dr. Oshima started her research career during her undergraduate years, where she studied folate metabolisms in clinical and basic research settings. This led her to pursue her doctoral degree from the University of South Alabama. Dr. Oshima’s dissertation project studied supernumerary arteries—vessels having markedly small diameters and acute branching angles—are prone to developing severe occlusive lesions in pulmonary arterial hypertension due to unusual hemodynamic stress caused by their structural properties.  

Dr. Oshima joined the laboratory of Dr. Schmidt at the University of Colorado as a post-doctoral fellow in 2016. Her post-doctoral work identified a novel contribution of endothelial glycocalyx remodeling to post-sepsis immunosuppression. As an independent investigator, she is interested in understanding how the structure of the endothelial glycocalyx impacts vascular functions. Her current project aims to delineate how coagulation is regulated by glycocalyx structures in health and disease, particularly in coagulopathy among patients with traumatic brain injury. Dr. Oshima’s research is funded by an American Heart Association Career Development award.  

Alicia Rizzo, MD, PhDAlicia Rizzo, MD, PhD 

Dr. Rizzo completed her undergraduate studies in neuroscience at Johns Hopkins University in 2009. She then completed her MD and a PhD in Pharmacology at the University of Illinois in 2017. Her thesis work tested the effects of the FDA approved chemotherapeutic agent imatinib mesylate in murine models of ARDS and elucidated the mechanisms by which the Abl family kinases mediate pulmonary vascular barrier function. She completed an Internal Medicine Residency and Pulmonary and Critical Care Fellowship at the University of Colorado.   

In 2020, she joined the Schmidt Laboratory as a post-doctoral research fellow. Her research in the Schmidt Laboratory investigates the role of the alveolar epithelial glycocalyx in ARDS using human airspace fluid samples obtained from heat moisture exchange filters and a complementary mouse model of targeted epithelial glycocalyx degradation. Dr. Rizzo was awarded grant funding for this work from NIH/National Heart, Lung, and Blood Institute (F32 NRSA and LRP) and the Colorado Clinical and Translational Sciences Institute. She was selected for the American Society for Clinical Investigation Emerging Generation Award in 2022. In 2023, she was awarded a Parker B. Francis Fellowship.  

Selected Publications

Schmidt EP, Yang Y, Janssen WJ, Gandjeva A, Perez MJ, Barthel L, Zemans RL, Bowman JC, Koyanagi DE, Yunt ZX, Smith LP, Cheng SS, Overdier KH, Thompson KR, Geraci MW, Douglas IS, Pearse DB, Tuder RM. The pulmonary endothelial glycocalyx regulates neutrophil adhesion and lung injury during sepsis. Nat Med. 2012; 18:1217-23 

Schmidt EP, Li G, Li L, Fu L, Yang Y, Overdier KH, Douglas IS, Linhardt RJ. The circulating glycosaminoglycan signature of respiratory failure in critically ill adults. J Biol Chem. 2014 Mar 21;289(12):8194-202. doi: 10.1074/jbc.M113.539452. Epub 2014 Feb 7. PMID: 24509853; PMCID: PMC3961648. 

Schmidt EP, Overdier KH, Sun X, Lin L, Liu X, Yang Y, Ammons LA, Hiller TD, Suflita MA, Yu Y, Chen Y, Zhang F, Cothren Burlew C, Edelstein CL, Douglas IS, Linhardt RJ. Urinary glycosaminoglycans predict outcomes in septic shock and ARDS. Am J Resp Crit Care Med. 2016, Aug 15;194(4):439-49. 

Yang Y, Haeger SM, Suflita MA, Zhang F, Dailey KL, Colbert JF, Ford JA, Picon MA, Stearman RS, Lin L, Liu X, Han X, Linhardt RJ, Schmidt EP. Fibroblast growth factor signaling mediates pulmonary endothelial glycocalyx reconstitution. Am J Respir Cell Mol Biol, 2017 Jun;56(6):727-37.  

Colbert JF, Ford JA, Haeger SM, Yang Y, Dailey KL, Allison KC, Neudecker V, Evans CM, Richardson VL, Brodsky KS, Faubel S, Eltzschig HK, Schmidt EP, Ginde AA. A model-specific role of microRNA-223 as a mediator of kidney injury during experimental sepsis. Am J Physiol Renal Physiol. 2017 Aug 1;313(2):F553-F559. doi: 10.1152/ajprenal.00493.2016. Epub 2017 May 17. PMID: 28515178; PMCID: PMC5582912. 

Zhang Y, Haeger SM, Yang Y, Dailey KL, Ford JA, Schmidt EP. Circulating Heparan Sulfate Fragments Attenuate Histone-Induced Lung Injury Independently of Histone Binding. Shock. 2017 Dec;48(6):666-673. doi: 10.1097/SHK.0000000000000907. PMID: 28538085; PMCID: PMC5685884. 

Haeger SM, Liu X, Han X, McNeil JB, Oshima K, McMurtry SA, Yang Y, Ouyang Y, Zhang F, Nozik-Grayck E, Zemans RL, Tuder RM, Bastarache JA, Linhardt RJ, Schmidt EP. Epithelial heparan sulfate contributes to alveolar barrier function and is shed during lung injury. Am J Respir Cell Mol Biol. 2018 Sep;59(3):363-374.  

Hippensteel JA, Anderson BJ, Orfila JE, McMurtry SA, Dietz RM, Su G, Ford JA, Yang Y, Zhang F, Hanx X, Yu Y, Liu J, Linhardt RJ, Meyer NJ, Herson PS, Schmidt EP. Circulating heparan sulfate fragments mediate septic cognitive dysfunction. J Clin Invest, 2019 April 1;129(4):1779-84.  

Zhang X, Han X, Xia K, Xu Y, Yang Y, Oshima K, Haeger SM, Perez MJ, McMurtry SA, Hippensteel JA, Ford JA, Herson PS, Liu J, Schmidt EP, Linhardt RJ. Circulating heparin oligosaccharides rapidly target the hippocampus in sepsis, potentially impacting cognitive functions. Proc Natl Acad Sci U S A. 2019 May 7;116(19):9208-9213. doi: 10.1073/pnas.1902227116. Epub 2019 Apr 22. PMID: 31010931; PMCID: PMC6511061. 

Hippensteel JA, Uchimido R, Tyler PD, Burke RC, Han X, Zhang F, McMurtry SA, Colbert JF, Lindsell CJ, Angus DC, Kellum JA, Yealy DM, Linhardt RJ, Shapiro NI, Schmidt EP. Intravenous fluid resuscitation is associated with septic endothelial glycocalyx degradation. Crit Care. 2019 Jul 23;23(1):259. doi: 10.1186/s13054-019-2534-2. PMID: 31337421; PMCID: PMC6652002. 

Oshima K, Han X, Ouyang Y, El Masri R, Yang Y, Haeger SM, McMurtry SA, Lane TC, Zhang F, Yue X, Vivès RR, Linhardt RJ, Schmidt EP. Loss of endothelial sulfatase-1 after experimental sepsis attenuates subsequent pulmonary inflammatory responses. Am J Physiol-Lung Cell Mol Physiol. 2019 Nov 1;317(5):L667-L677. 

LaRivière WB, Liao S, McMurtry SA, Oshima K, Han X, Zhang F, Yan S, Haeger SM, Ransom M, Bastarache JA, Linhardt RJ, Schmidt EP (corresponding author), Yang Y. Alveolar heparan sulfate shedding impedes recovery from bleomycin-induced lung injury. Am J Physiol Lung Cell Mol Physiol. 2020 Jun 1;318(6):L1198-L1210 

Rizzo AN, Haeger SM, Oshima K, Yang Y, Wallbank AM, Jin Y, Lettau M, McCaig LA, Wickersham N, McNeil JB, Zakharevich I, McMurtry SA, Langouët-Astrié CJ, Kopf KW, Voelker DR, Hansen K, Shaver CM, Kerchberger VE, Peterson RA, Kuebler WM, Ochs M, Veldhuizen RAW, Smith BJ, Ware LB, Bastarache JA, Schmidt EP. Alveolar epithelial glycocalyx degradation mediates surfactant dysfunction and contributes to acute respiratory distress syndrome. JCI Insight. 2022 Jan 25;7(2):e154573. 

Langouët-Astrié C, Oshima K, McMurtry SA, Yang Y, Kwiecinski JM, LaRivière WB, Kavanaugh JS, Zakharevich I, Hansen KC, Shi D, Zhang F, Boguslawski KM, Perelman SS, Su G, Torres VJ, Liu J, Horswill AR, Schmidt EP. The influenza-injured lung microenvironment promotes MRSA virulence, contributing to severe secondary bacterial pneumonia. Cell Rep. 2022 Nov 29;41(9):111721. doi: 10.1016/j.celrep.2022.111721. PMID: 36450248. 

Colbert JF, Kirsch JM, Erzen CL, Langouët-Astrié CJ, Thompson GE, McMurtry SA, Kofonow JM, Robertson CE, Kovacs EJ, Sullivan RC, Hippensteel JA, Sawant NV, De Nisco NJ, McCollister BD, Schwartz RS, Horswill AR, Frank DN, Duerkop BA, Schmidt EP. Aging-associated augmentation of gut microbiome virulence capability drives sepsis severity. mBio. 2023 Apr 27:e0005223. doi: 10.1128/mbio.00052-23.

Schmidt Lab Alumni

Previous Postdoctoral Fellows and PhD Students: 

  • Sarah Haeger, MD, PhD (2014-2018): Internal Medicine Chief Resident, University of Colorado 
  • James Colbert, MD (2014-2018): Assistant Professor of Medicine, University of Colorado 
  • Joe Hippensteel, MD (2016-2019): Assistant Professor of Medicine, University of Colorado  
  • Wells LaRiviere, MD, PhD (2017-2021): Surgery Resident, University of Colorado 
  • Christophe Langouet Astrie, PhD (2019-2022): Postdoctoral Research Fellow, University of Washington  
  • Ryan Sullivan, MD, MS (2021-2023): Postdoctoral Fellow, University of Colorado 

Laboratory Scientists and Alumni: 

  • Sarah McMurtry, PhD  
  • Sumei Liao, PhD  
  • Shuaiguo Yan, PhD  
  • Sam King, MD  
  • Melissa New, MD  
  • Aaron Nadon, MD  
  • Igor Zakhavevich   
  • Joshay Ford  
  • Carsten Michael   
  • Grace Thompson